Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials of Pharmacotherapy

Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial — N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.     

Changing Pattern of Sputum Cell Counts During Successive Exacerbations of Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease exacerbations are associated with worsening of airway inflammation, the nature of which may be neutrophilic, eosinophilic, or both.

Objective: The primary objective was to examine the cellular nature of airway inflammation in successive COPD exacerbations in order to ascertain if they changed in individual patients. The secondary objective was to estimate the relative risk indicating the extent to which a particular type of exacerbation changed as a function of the most recent exacerbation. Design: This was a retrospective survey performed on a computerised sputum cell count database of a referral respiratory service in Hamilton, Canada. Recurrent event analyses were used to model the incidence of exacerbations and subtypes of exacerbations. Results: 359 patients and 148 patients had sputum examined during stable condition and during exacerbations, respectively. It was found 65 patients had sputum examined during both situations. The exacerbations were eosinophilic in 15.9%, neutrophilic in 18%, combined in 2.6%, of unknown clinical significance in 19.6% and normal in 19.6%. There were missing counts for 24.3% samples. In 85.2% of patients, a different subtype of bronchitis was noted in successive exacerbations. The relative risk of a subsequent neutrophilic or eosinophilic exacerbation was 6.24 (p = 0.02) and 2.8 (p = 0.24) when the previous exacerbation was neutrophilic or eosinophilic respectively. Conclusions: This non-intervention study suggests that the cellular nature of bronchitis is largely unpredictable and needs to be examined at each COPD exacerbation This has important implications in choosing the appropriate therapy. Future intervention studies would provide further evidence.     

Breathlessness or Health Status in Chronic Obstructive Pulmonary Disease: The Impact of Different Definitions

Objective: The GOLD 2011 report recommends the use of symptoms, exacerbation history, and FEV1% predicted to categorise patients into groups A–D. We investigated the choice of mMRC or CAT on category assignment and characterization of the categories. Methods: Patients were prospectively recruited from tertiary hospitals in China, as part of the INTACT study, with a prior diagnosis of COPD. The GOLD categories were defined using mMRC and CAT, along with exacerbations in the previous year, and FEV1% predicted. Results: 1,465 patients were included. The most prevalent group was group D. However, proportions of patients categorised into groups A to D differed depending on symptom instruments. The use of CAT resulted in more patients being placed into groups B and D. Cardiac co-morbid conditions, particularly ischaemic heart disease, heart failure, and arrhythmia were highly prevalent in groups B and D. Group B appeared to have a similar burden of cardiac co-morbidities to group D, in spite of a higher FEV1 level. Although mMRC assigned a smaller proportion of patients to groups B and D, the patients it did assign had a higher burden of cardiac co-morbidities than patients assigned by CAT. When patients were assessed according to LLN, 14.2% had normal airflow according to ECSC 1993 equations, with 12.6% having normal airflow according to GLI 2012 formulae. Conclusions: The choice of symptom assessment is one potential confounder impacting the patient assignment. Breathlessness may be an important marker of overall disease severity, indicating the presence of cardiac co-morbidities in the GOLD categories.     

Red Blood Cell Distribution and Survival in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Background: Cardiovascular disease (CVD) contributes significantly to mortality in chronic obstructive pulmonary disease (COPD). Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity that is largely overlooked, is a newly recognized mortality marker in patients with established CVD. It is unknown whether RDW is associated with mortality in COPD patients.

Aims: To study the prognostic value of RDW in patients with COPD and to compare the value of this measurement with cardiac, respiratory, and hemotological status. Method: We performed retrospective analyses of 270 patients stable with COPD who were admitted to our hospital between January 2007 and December 2009. Demographic, clinical, echocardiographic, and laboratory characteristics were registered and recorded COPD deaths were registered as outcomes. Results: In the overall patients, the RDW level had a mean value of 15.1 ± 2.4. RDW was positively correlated with C-reactive protein (CRP) (p = 0.008, r = 0.21), right ventricular dysfunction (RVD) (p < 0.001, r = 0.25), and pulmonary arterial hypertension (PAH) (p = 0.03, r = 0.14). Variables (p < 0.1) included in the univariate survival analysis were forced expiratory volume in 1 second (FEV1% predicted), RDW levels, age, PaCO2, albumine and CRP levels, presence of CVD, presence of anemia, presence of RVD, and presence of PAH. Subsequent multivariate analysis suggested that RDW levels (1.12; 95% CI, 1.01 to 1.24; p = 0.01), and presence of RVD (2.6; 95% CI, 1.19 to 5.8; p = 0.01) were independently related to mortality. Conclusion: Elevated RDW levels were associated with increased mortality risk in stable COPD patients.     

Asthma,Chronic Obstructive Pulmonary Disease,and Mortality in the U.S. Population

Background: COPD and asthma are common diseases in the U.S. population and can coexist. Our goal was to determine the prevalence of self-reported, physician-diagnosed asthma and COPD in a sample of the U.S. population and their association with lung function impairment and mortality. Methods: We used baseline data from NHANES III and the follow-up mortality data. We used logistic regression and Cox Proportional Hazards models, adjusting for age, sex, race/ethnicity, education level, smoking status, and disease stage. Results: The sample consisted of 15,203 subjects, of whom 4,542 died during the follow-up period. Coexisting COPD and asthma was reported by 357 (2.7%), COPD by 815 (5.3%), and asthma by 709 (5.3%). Subjects with both conditions had a higher proportion of obstruction (30.9%) than those with COPD (24.3%), asthma (13.3%), or no lung disease (5.4%). In survival models adjusting for all factors except baseline lung function, coexisting COPD and asthma had the highest risk for mortality (Hazard Ratio [HR] 1.83, 95% confidence interval [CI] 1.34, 2.49), followed by COPD only (HR 1.44, 95% CI 1.28, 1.62), and asthma only (HR 1.16, 95% CI 0.94, 1.42). These affects were attenuated after controlling for baseline lung function: coexisting asthma and COPD (HR 1.45, 95% CI 1.06, 1.98), COPD only (1.28, 95% CI 1.13, 1.45), and asthma only (HR 1.04, 95% CI 0.85, 1.27). Conclusion: In this analysis, subjects who report coexisting asthma and COPD have a higher risk of obstruction on spirometry and a higher risk of death during follow-up.     

老年慢性阻塞性肺病支原体感染的研究

应用聚合酶链反应（PCR）技术检测了60例老年慢性阴塞性肺病（COPD）患者的临床标本（咽部分泌物）．结果发现10例肺炎支原体（MP）阳性，同时对这10例阳性者用酶联免疫法（ELISA）检测其血清抗体予以对照，发现4例为阴性．提示MP感染是COPD急性发作的重要原因之一，而PCR技术可以快速、灵敏地检测COPD急性发作时MP感染，其检出率高于用ELISA法．     

Geographic Variation in Chronic Obstructive Pulmonary Disease Exacerbation Rates

Background Exacerbations are important disease events for patients with chronic obstructive pulmonary disease (COPD) as they are relatively frequent, result in significant resource use and can indicate worsening disease. Little is known about variation in COPD exacerbation rates across a health system in various geographic regions. Objective To compare COPD exacerbation rates by regional service networks called Veterans Integrated Service Network (VISN) in the Veterans Health Administration (VA) system. Design Retrospective, observational study. Subjects Patients with a COPD diagnosis from October 1999 to September 2000 with follow-up to September 2002. Measurements Acute exacerbations of COPD during the baseline and follow-up periods. Results A total of 198,981 patients were identified. Average exacerbation rate at baseline was 0.503 events per person per year. In the follow-up period, there were 187,686 exacerbations experienced by 87,494 persons (44.0% of cohort). During follow-up, the average adjusted exacerbation rate was 0.589 per person per year and varied from 0.335 (95% CI, 0.328–0.342) in VISN 1 to 0.749 (95% CI, 0.735–0.0.763) in VISN 9. Using the median rate of exacerbation during the baseline period as the referent, 9 VISNs had lower adjusted rate ratios and 12 VISNs had higher adjusted rate ratios in the follow-up period. Conclusions Geographic variation in the VA VISN system supports evidence that the medical care system including provider factors, and less so patient factors, affect COPD exacerbations. Understanding the reasons underlying this variation in COPD exacerbation rates may lead to improvements in future care and outcomes.     

Early Supported Discharge/Hospital At Home For Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Review and Meta-Analysis

A systematic review and meta-analysis was performed to assess the safety, efficacy and cost of Early Supported Discharge (ESD) and Hospital at Home (HAH) compared to Usual Care (UC) for patients with acute exacerbation of COPD (AECOPD). The structure of ESD/HAH schemes was reviewed, and analyses performed assuming return to hospital during the acute period (prior to discharge from home treatment) was, and was not, considered a readmission. The pre-defined search strategy completed in November 2014 included electronic databases (Medline, Embase, Amed, BNI, Cinahl and HMIC), libraries, current trials registers, national organisations, key respiratory journals, key author contact and grey literature. Randomised controlled trials (RCTs) comparing ESD/HAH to UC in patients admitted with AECOPD, or attending the emergency department and triaged for admission, were included. Outcome measures were mortality, all-cause readmissions to 6 months and cost. Eight RCTs were identified; seven reported mortality and readmissions. The structure of ESD/HAH schemes, particularly selection criteria applied and level of support provided, varied considerably. Compared to UC, ESD/HAH showed a trend towards lower mortality (RR_MH = 0.66; 95% CI 0.40–1.09, p = 0.10). If return to hospital during the acute period was not considered a readmission, ESD/HAH was associated with fewer readmissions (RR_MH = 0.74, 95% CI: 0.60–0.90, p = 0.003), but if considered a readmission, the benefit was lost (RR_MH = 0.84; 95% CI 0.69–1.01, p = 0.07). Costs were lower for ESD/HAH than UC. ESD/HAH is safe in selected patients with an AECOPD. Further research is required to define optimal criteria to guide patient selection and models of care.     

Factors Associated With Outcomes of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

The purpose of this article is to provide a general review of the current literature on the factors associated with the outcomes of hospitalizations, survival and health‐related quality of life in acute exacerbations of chronic obstructive pulmonary disease (AECOPD), highlighting the limitations and the complexities in interpretation of the results of current studies. There is no consensus definition for AECOPD; onsets may be difficult to define and the determination of duration elusive. The prevalence of acute exacerbations of COPD (AECOPD) in the community appears to be underestimated as exacerbations are underreported by patients and their doctors. Hospitalization for COPD is due mainly to severe AECOPDs which drive the cost of care. There are few longitudinal epidemiological studies on factors associated with hospitalizations for AECOPD. The results of current studies do not allow clear differentiation between associations that are predictors of event, the consequences of the event, or indicators of severity. Strategies to reduce severe exacerbations of COPD include pharmacological treatment, vaccinations, pulmonary rehabilitation, and home care programs. The optimal strategy for the reduction of hospitalization in COPD remains unclear. Long-term interventional studies are needed to provide clearer information for the prevention of exacerbations and hospitalizations in COPD.     

The Relationship between Particulate Matter (PM10) and Hospitalizations and Mortality Of Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Abstract

Background: Numerous studies have reported variable associations between ambient particulate matter (PM) and chronic obstructive pulmonary disease (COPD) hospitalizations and mortality. Objective: To conduct a systematic study assessing the associations between hospitalizations and mortality from COPD and ambient PM₁₀ (particulate matter with aerodynamic diameters ≤ 10 μm, PM₁₀). Methods: Systematic searches were conducted in 6 common electronic databases. A meta-analysis was performed to estimate the odds ratio (OR) to evaluate the relationship between PM₁₀ and COPD hospitalizations and mortality. Publication bias and heterogeneity of samples were tested by Begg funnel plot and Egger test, respectively. Study findings were analyzed using random-effect model and fixed-effect model. Results: The search yielded 31 studies suitable for the meta-analysis during the period from Jan 1, 2000 to Oct 31, 2011. A 10μg/m³ increase in PM₁₀ was associated with a 2.7% (95%CI = 1.9%-3.6%) increase in COPD hospitalizations with an OR of 1.027 (95%CI: 1.019–1.036), and a 1.1% (95%CI: 0.8%–1.4%) increase in COPD mortality with an OR of 1.011 (95%CI: 1.008–1.014). Conclusions: Ambient PM₁₀ is associated with increased COPD hospitalizations and mortality. Further research is needed to elucidate whether this association is causal and to clarify its mechanisms.